In a study of 423 men on TST, Ranjith Ramasamy, MD, working with Larry Lipshultz, MD, at the Baylor College of Medicine in Houston, measured subjects' testosterone and estradiol levels and asked the men to rate the quality of their libido using a five-point Likert scale (1= terrible, 5 = excellent). The researchers categorized the men as having low or high testosterone (below or above 300 ng/dL, respectively) and low or high estradiol (below 5 and above 5 ng/dL, respectively).

Men with high serum testosterone levels reported significantly greater libido than men with low level and those with high serum estradiol levels had significantly greater libido than subjects with low levels. In all, 60.4% of men with both high testosterone and estradiol levels reported very good or excellent libido (score as 4 or 5) compared with 31.3% of participants with both low testosterone and estradiol levels, the researchers reported in European Urology (published online ahead of print). These results are expected to be presented at the American Urological Association annual meeting in Orlando this May.

In multivariable analysis, men with high levels of estradiol were twice as likely as those with low levels to report very good or excellent libido, according to the investigators. Although their study highlights the importance of estrogen in men on TST, the authors explained, limitations include a lack of a control group and absence of score comparisons before and after start of TST. They also noted that a larger sample size might have unmasked a confounding relationship between testosterone and libido.

“Estradiol plays an important role in libido in men taking testosterone supplementation,” Dr. Ramasamy said, adding that this finding is similar to what was identified in a recently published study by Joel S. Finkelstein, MD, and collaborators at Massachusetts General Hospital in Boston. The study, which was published in the New England Journal of Medicine (2013;369:1011-1022), showed that libido declines dramatically in conjunction with decreased levels of serum estrogen.

Additionally, the study demonstrated that testosterone deficiency in men accounts for decreases in lean mass, muscle size, and strength, whereas estrogen deficiency primarily accounts for increases in body fat.

“Aromatase inhibitors to reduce estrogen should be used judiciously to treat symptoms, such as gynecomastia and breast tenderness, and not for the sole purpose of reducing a high estrogen laboratory value,” Dr. Ramasamy cautioned.